Studies are to be carried out to determine the pathophysiology and effects on the central nervous system of lactic acidosis. Animal models of both primary (spontaneous) and secondary lactic acidosis have been developed in laboratory animals. In addition to studying the pathophysiology of lactic acidosis, effects of specific therapeutic modalities on these disease states will also be evaluated. Such therapy will include bicarbonate, methylene blue, glucose and insulin, vasodilators, and dialysis. The parameters to be evaluated include measurements of intracellular pH in skeletal muscle, liver and brain; redox potential in liver and brain; osmolality and contents of Na ion, K ion, Cl-, lactate and pyruvate in CSF, plasma and brain, and arterio-venous oxygen gradients across both cerebral and peripheral circulation. It is hoped that elucidation of the pathophysiology and effects on the central nervous system of lactic acidosis will lead to a rational therapeutic approach to this condition. Effects on the central nervous system of diabetic ketoacidosis and its treatment will also be evaluated. Particular emphasis will be placed on the pathophysiology of coma, and the mechanisms whereby cerebral edema may develop in patients being treated for ketoacidosis. An animal model of diabetic ketoacidosis has been developed. Parameters to be evaluated include brain intracellular pH, Na ion, K ion, Cl-, H2O and osmolality, as well as the electroencephalogram of normal, diabetic and ketoacidotic animals.